Department of Urology, The Affiliated Changzhou No 2. Hospital of Nanjing Medical University, Changzhou, Jiangsu, China.
PLoS One. 2013 Aug 27;8(8):e73700. doi: 10.1371/journal.pone.0073700. eCollection 2013.
Disruption of apoptosis has been implicated in carcinogenesis. Specifically, various single-nucleotide polymorphisms (SNPs) in apoptotic genes, such as FAS-1377 G/A SNP, have been associated with cancer risk. FAS-1377 G/A SNP has been shown to alter FAS gene promoter transcriptional activity. Down-regulation of FAS and cell death resistance is key to many cancers, but an association between FAS-1377 G/A SNP and cancer risk is uncertain. Therefore, we conducted a meta-analysis of the current literature to clarify this relationship.
METHODOLOGY/PRINCIPAL FINDINGS: From PubMed and Chinese language (CNKI and WanFang) databases, we located articles published up to March 5, 2013, obtaining 44 case-control studies from 41 different articles containing 17,858 cases and 24,311 controls based on search criteria for cancer susceptibility related to the FAS gene -1377 G/A SNP. Odds ratios (ORs) and 95% confidence intervals (CI) revealed association strengths. Data show that the -1377 G allele was protective against cancer risk. Similar associations were detected in "source of control," ethnicity and cancer type subgroups. Lower cancer risk was found in both smokers with a GG+GA genotype and in non-smokers with the GG+GA genotype, when compared to smokers and nonsmokers with the AA genotype. Males carrying the -1377G allele (GG+GA) had lower cancer incidence than those with the AA genotype. Individuals who carried both FAS-1377(GG+GA)/FASL-844(TT+TC) genotypes appeared to have lower risk of cancer than those who carried both FAS-1377 AA/FASL-844 CC genotypes.
CONCLUSIONS/SIGNIFICANCE: The FAS-1377 G/A SNP may decrease cancer risk. Studies with larger samples to study gene-environment interactions are warranted to understand the role of FAS gene polymorphisms, especially -1377 G/A SNP, in cancer risk.
细胞凋亡的中断与癌变有关。具体而言，凋亡基因（如 FAS-1377 G/A 单核苷酸多态性（SNP））的各种 SNP 与癌症风险相关。已经表明，FAS-1377 G/A SNP 改变了 FAS 基因启动子转录活性。FAS 的下调和细胞死亡抵抗是许多癌症的关键，但 FAS-1377 G/A SNP 与癌症风险之间的关联尚不确定。因此，我们对当前文献进行了荟萃分析以阐明这种关系。
方法/主要发现：我们从 PubMed 和中文（CNKI 和万方）数据库中检索到截至 2013 年 3 月 5 日发表的文章，根据与 FAS 基因-1377 G/A SNP 相关的癌症易感性搜索标准，从 41 篇不同文章中获得了包含 17858 例病例和 24311 例对照的 44 项病例对照研究。比值比（OR）和 95％置信区间（CI）揭示了关联强度。数据表明，-1377 G 等位基因可预防癌症风险。在“对照来源”、种族和癌症类型亚组中也检测到类似的关联。与 AA 基因型的吸烟者和非吸烟者相比，GG+GA 基因型的吸烟者和非吸烟者的癌症风险较低。携带-1377G 等位基因（GG+GA）的男性比携带 AA 基因型的男性癌症发病率更低。与携带 FAS-1377（AA）/FASL-844（TT+TC）基因型的个体相比，携带 FAS-1377（GG+GA）/FASL-844（TT+TC）基因型的个体癌症风险较低。
结论/意义：FAS-1377 G/A SNP 可能降低癌症风险。需要进行更大样本的研究以研究基因-环境相互作用，以了解 FAS 基因多态性（特别是-1377 G/A SNP）在癌症风险中的作用。
